Manufacturing, Characterization and Evaluation of the Effect of Silk Fibroin Membranes, Loaded or Not With Neurotensins on Open Wounds in the Palate

January 12, 2022 updated by: Mauro Pedrine Santamaria, Universidade Estadual Paulista Júlio de Mesquita Filho

Manufacturing, Characterization and Evaluation of the Effect of Silk Fibroin Membranes, Loaded or Not With Neurotensins on Open Wounds in the Palate: Randomized Clinical Study

The aim of the present study will be to manufacture and characterize silk fibroin membranes loaded or not with neurotensin and to evaluate clinical, patient-centered and immunological parameters the effect of using these membranes on open wounds on the human palate.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Surgical procedures for the reconstruction of gingival and peri-Implant tissues with the purpose of restoring function and aesthetics are commonly used in the dental practice. The use of free gingival graft (FGG), despite being considered the gold standard, causes great morbidity and postoperative pain. Thus, in order to reduce these complications, some biomaterials have been explored to accelerate healing and bring greater comfort to the patient. The present study aims to: 1. manufacture silk fibroin membranes (SF), loaded or not with neurotensin (NT); 2. evaluate, clinically and immunologically, the effect of the membranes on open wounds at palate sites. After the manufacture of the membranes they will be characterized by visual aspect, thickness, mechanical properties, surface texture, water vapor permeability, enzymatic degradation and swelling. Posteriorly, sixty six (n = 66) patients requiring exodontia and ridge preservation for future implant placement will be randomly assigned into three groups: Control - Free Gingival Graft (n = 22): extraction and Free Gingival Graft for sealing the alveolus entrance; Group SF - Fibroin membrane (n = 22): extraction and Free Gingival Graft for sealing the alveolus entrance and placement of the fibroin membrane at the palatal wound site; Group SF + NT - Free Gingival Graft + Neurotensin-loaded Fibroin Membrane (n = 22): extraction and Free Gingival Graft for sealing the alveolus entrance and placement of neurotensin-loaded fibroin membrane at the palatal wound site. The repair of the palatine donor area will be evaluated by clinical parameters such as remaining wound area, tissue thickness, re-epithelialization and early-wound healing index at baseline, 7, 14, 21, 30, 45, and 90 days after the procedure; and patient-centered outcomes by post-operative discomfort, tissue edema and number of analgesic pills used for 14 days after the procedure. In addition, inflammatory cytokines and growth factors will be assessed using the palatal wound inflammatory exudate 3 and 7 days after surgery. For the descriptive statistics, the mean ± standard deviation will be used; Normality: Shapiro-Wilk test; Clinical trials: ANOVA for intra and inter group calculations + Tukey test for multiple comparisons when the Shapiro-Wilk p value ≥ 0.05. If p Shapiro-Wilk <0.05, will be analyzed using the Friedman test (intragroup) and Mann-Whitney tests (intergroup); Parameters centered on patients: T test.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

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Study Locations

  • Brazil
    • Sao Paulo
      • São José Dos Campos, Sao Paulo, Brazil, 12245000
        • Recruiting
        • Mauro Pedrine Santamaria and Ana Carolina Ferreira Bonafe

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients at least 18 years old, healthy systemically, with good oral hygiene, assessed by means of a plaque index and gingival index less than 25% (O'Leary et al., 1972)
  • Patients with no morphological or pathological changes in the donor palatal region;
  • Patients who have an indication for extraction and with an indication to preserve the socket for future implant installation;
  • The tooth included in the study, as well as the adjacent teeth, must not have loss of periodontal insertion.

Exclusion Criteria:

  • Patients with systemic problems (cardiovascular changes, blood dyscrasias, immunodeficiency, diabetes, among others), who contraindicate the surgical procedure;
  • Patients who use medications that interfere with wound healing;
  • Pregnant or lactating patients;
  • Patients who present opportunistic oral lesions, mainly colonizing the palate region;
  • Smoking patients;
  • Patients undergoing orthodontic treatment;
  • Patients already submitted to periodontal surgery in the area of interest in the present study;
  • Patients with a history of allergy to any type of material used in the present study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Control Group (CG)
The palatal wound area will not receive any treatment
Procedure: Palatal Wound
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures.
Experimental: Silk Fibroin Film - SF
The palatal wound area will receive silk fibroin film as a dressing
Procedure: Palatal Wound
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures.
Device: Palatal Wound treated with Silk Fibroin Film
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive a silk fibroin film and 4.0 silk sutures.
Experimental: Neurotensin-loaded Silk Fibroin Film - SF + NT
The palatal wound area will receive a neurotensin-loaded silk fibroin film as a drug delivery system
Procedure: Palatal Wound
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures.
Device: Palatal Wound treated with Neurotensin-loaded Silk Fibroin Film
With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive a silk fibroin film loaded with neurotensin and 4.0 silk sutures.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the Remaining Wound Area (RWA)
Time Frame: baseline, 7, 14, 21, 30, 45 and 90 days after surgery
For this, standardized photographs will be taken. As a reference, a scale will be used to measure this area. These photographs will be exported to image software (Image J - National Institute of Health -NIH, Bethesda, USA), the area of the wound will be measured in square millimeters (Dias et al. 2015)
baseline, 7, 14, 21, 30, 45 and 90 days after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tissue Thickness
Time Frame: baseline, 45 and 90 days after the procedure
An endodontic spacer (Dentsply-Maillefer Instruments S.A. - Switzerland) with a rubber cursor will be placed in contact with the area until the palatal bone is reached, without pressing the tissue. The distance between the tip of the spacer and the cursor will be measured using a digital caliper (Dias et al., 2015).
baseline, 45 and 90 days after the procedure
Scar and Tissue Colorimetry
Time Frame: 7, 14, 21, 30, 45 and 90 postoperative days
The presence or absence of scar or keloid in the operated area will be analyzed. In addition, the tissue color similarity of regions adjacent to the operated area and postoperative images will be analyzed through photographs. The photographs will be exported to image software (Adobe Photoshop, München, Germany), using two areas, the wound and one adjacent. The comparison (ΔE) of the areas will be made using brightness parameters (L), red-green chroma scale and blue-yellow chroma scale (b) according to the following equation (Knösel et al., 2009): ΔE =[(L.wound - L.adjacent)2 + (a.wound - a.adjacent)2 + (b.wound - b.adjacent)2] 1/ 2
7, 14, 21, 30, 45 and 90 postoperative days
Epithelialization
Time Frame: baseline, 3, 7, 14 and 30 days after the procedure
The wound will be colored with Shirley's solution and the epithelialized area will be quantified in the Image J. program. Then, with the total wound area, the % epithelialization will be calculated (Ozcelik et al., 2008).
baseline, 3, 7, 14 and 30 days after the procedure
Early wound healing index
Time Frame: 7 and 14 days after surgery

Any changes in wound healing will be evaluated, with five different degrees:

  • Complete wound closure with absence of fibrin on the palate;
  • Complete wound closure with the presence of a fibrin line on the palate;
  • Complete wound closure with the presence of a fibrin clot on the palate;
  • Incomplete wound closure with partial tissue necrosis on the palate;
  • Incomplete wound closure with total tissue necrosis on the palate.
7 and 14 days after surgery
Tissue edema
Time Frame: 7 days after the surgical procedure
It will be evaluated with the score: 1 = absent; 2 = slight; 3 = moderate; or 4 = severe (Sanz-Moliner et al. 2013).
7 days after the surgical procedure
Postoperative discomfort
Time Frame: 7, 14, 21, 30, 45 and 90 days after the surgical procedure
Sensitivity will be measured by air spray for 5 s over the palatal region. After the air spray, patients will be required to use a 100 mm visual analog scale (VAS) to assess discomfort, where the extremes of the scale will be "none" and "extreme" to report the discomfort of this measure (Dias et al. 2015)
7, 14, 21, 30, 45 and 90 days after the surgical procedure
Number of analgesics
Time Frame: until 14 days after surgery
Patients will be given a postoperative diary in which they will note their pain intensity on a visual analog scale (VAS) 100 mm and the number of painkillers used (Tonetti et. al 2017).
until 14 days after surgery
Immunologic Analysis - cytokines
Time Frame: 3 and 7 days after surgery
The inflammatory exudate present in the palate open wound region will be collected. Samples will be obtained by placing strips of filter paper for 40 s (PerioPaper, Oraflow, New York, USA) in contact with the open wound. After the volume measurements (Periotron 8000, Oraflow, New York, USA), the strips will be placed in sterile tubes containing 300 ml of phosphate buffered saline (PBS) with 0.05% Tween-2 and stored immediately at -80 ° C. Strips contaminated with visible blood will be discarded. The following cytokines will be evaluated: Interleukin-1β (IL1β), Interleukin-4 (IL4), Interleukin-5 (IL5), Interleukin-6 (IL6), Interleukin-9 (IL9), Interleukin-10 (IL10), Interleukin-17A (IL17A), and tumor necrosis factor alpha (TNFα).
3 and 7 days after surgery
Immunologic Analysis - growth factors
Time Frame: 3 and 7 days after surgery
The inflammatory exudate present in the palate open wound region will be collected. Samples will be obtained by placing strips of filter paper for 40 s (PerioPaper, Oraflow, New York, USA) in contact with the open wound. After the volume measurements (Periotron 8000, Oraflow, New York, USA), the strips will be placed in sterile tubes containing 300 ml of phosphate buffered saline (PBS) with 0.05% Tween-2 and stored immediately at -80 ° C. Strips contaminated with visible blood will be discarded. The following growth factors will be evaluated: Epidermal growth factor (EGF), Transforming growth factor beta (TGF-β), Platelet-derived growth factor (PDGF), Fibroblast growth factors (FGF), and Vascular endothelial growth factor (VEGF).
3 and 7 days after surgery
Immunologic Analysis - matrix metalloproteinases
Time Frame: 3 and 7 days after surgery
The inflammatory exudate present in the palate open wound region will be collected. Samples will be obtained by placing strips of filter paper for 40 s (PerioPaper, Oraflow, New York, USA) in contact with the open wound. After the volume measurements (Periotron 8000, Oraflow, New York, USA), the strips will be placed in sterile tubes containing 300 ml of phosphate buffered saline (PBS) with 0.05% Tween-2 and stored immediately at -80 ° C. Strips contaminated with visible blood will be discarded. The following Matrix metalloproteinases will be evaluated: matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), and Tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1/TIMP-2).
3 and 7 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universidade Estadual Paulista Júlio de Mesquita Filho

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Mauro P Santamaria, Sao Paulo States University - Brazil
  • Principal Investigator: Ana Carolina F Bonafe, Sao Paulo States University - Brazil

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 21, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 13, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 13, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UEPJMF 12

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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